Over a quarter century of research has significantly improved our understanding of the circulating cardiovascular system and its cellular components. However, study of the parallel lymphatic system has lagged far behind, limiting our understanding of this complex and potentially clinical beneficial network. The lymphatic system is comprised of an extensive network of vessels and nodes that parallel the venous vasculature. Peripheral lymphatic channels combine to form a single thoracic duct that enters the venous system at the confluence of the left internal jugular and subclavian veins. It is known that the lymphatic system plays a number of roles in GI physiology including fluid homeostasis, digestion, and cell mediated immunity. More recent research suggests potentially critical roles in pathophysiological conditions such as diabetes, cancer, cirrhosis, and autoimmune disorders. A significant obstacle in advancing lymphatic research is the ability to safely and easily collect circulating lymph and its cellular components. The majority of studies on circulating lymphatic cells depend on cells collected from peripheral blood, where lymphocytes make up less than 3% of circulating cells. Peripheral blood collection techniques (the predominant type is leukapheresis) are time consuming and expensive. Processing can damage cells, altering their genetic profile and impacting behavior. Because of the complexity and time required, it is difficult to obtain multiple scheduled samples and truly map changes in lymphocyte populations and non-cellular components in real-time. Direct sampling from the lymphatic system requires a complex open surgical cut-down to locate and cannulate the thoracic duct which is not feasible for widespread clinical use, particularly in a research setting. We are proposing a novel sampling method to access and aspirate lymphocytes, fluid, and non-cellular components directly from the thoracic duct. Our approach involves a novel access catheter placed via the central venous system under ultrasound visualization. Catheterization is safe and predictable, leveraging existing central venous access and guidewire techniques. Access would provide an exponentially higher concentration of desirable cell types. This Phase II project is divided into two Specific Aims. Our preliminary studies and existing data on lymphatic anatomy and physiology suggests it will be critical in many downstream applications that our device is safe and effective over a dwell time sufficient to collect a sizable number of potentially rare cell types, re- infuse drugs or cells, or monitor the immune system during illness, transplantation, or drug administration. In Aim I we will refine our design to facilitate longer dwell times which permit intermittent, chronic aspiration and infusion. Designs will be validated first in benchtop models and later in a large animal study. In Aim II we will undertake mechanical and biocompatibility testing required for clinical use and FDA approval. Regulatory strategy and planning are included in this approach. Completion of these activities will place the company in a position to move efficiently through regulatory approval and into clinical use.